DESCRIPTION(Verbatim from the Applicant's Abstract): Spinal networks that produce locomotor-like rhythmic electrical activity are formed at early stages of neuronal differentiation in the rat spinal cord. Previous studies have suggested that each side of the spinal cord contains a group of spinal interneurons that form a network referred to as the central pattern generator, which produces rhythmic electrical activity independently of supraspinal and peripheral sensory inputs. The coordinated oscillatory potentials in opposite sides of the spinal cord are thought to be responsible for the left/right alternating hind limb movements. The primary goal of this application is to determine the developmental changes in the organization and functional integration of distinct neural networks that trigger rhythmic electrical activity and coordinate bilateral activity in the developing mammalian spinal cord. Real-time images of voltage-sensitive fluorescent dye will be used to record changes in electrical activity in various areas of the isolated spinal cord. The main objectives of our application are: (1) To characterize the changes in the spatiotemporal pattern of spontaneous coordinated rhythmic oscillations during embryonic and postnatal development, and study the properties of the potential underlying those activities. (2) To investigate the spatial organization and functional integration of rhythm-generating networks and networks that coordinate the oscillatory electrical activity between the ipsilateral and contralateral sides of the spinal cord. Mechanical lesions at specific sites and local pharmacological block of synaptic transmission will be used to test the role of specific pathways in the generation of locomotor-like activity. (3) To determine the functional relationship between neural pathways that mediate spontaneous and pharmacologically induced rhythmic oscillations at the onset of coordinated bilateral activity. Experiments will be carried out using complementary biophysical and electrophysiological approaches in thick spinal cord slices in which neural networks are preserved. These studies will increase our understanding of the mechanisms underlying the establishment of rhythm-generating networks and the complex functional integration of rhythmic activity that results in bilateral coordinated activity. The findings will be valuable for gaining insight into factors that might regulate long-term cellular interactions and synaptic plasticity in mature neural networks.